High-flow nasal oxygen for children's airway surgery to reduce hypoxaemic events: a randomised controlled trial.

BACKGROUND: Tubeless upper airway surgery in children is a complex procedure in which surgeons and anaesthetists share the same operating field. These procedures are often interrupted for rescue oxygen therapy. The efficacy of nasal high-flow oxygen to decrease the frequency of rescue interruptions in children undergoing upper airway surgery is unknown. METHODS: In this multicentre randomised trial conducted in five tertiary hospitals in Australia, children aged 0-16 years who required tubeless upper airway surgery were randomised (1:1) by a web-based randomisation tool to either nasal high-flow oxygen delivery or standard oxygen therapy (oxygen flows of up to 6 L/min). Randomisation was stratified by site and age (<1 year, 1-4 years, and 5-16 years). Subsequent tubeless upper airway surgery procedures in the same child could be included if there were more than 2 weeks between the procedures, and repeat surgical procedures meeting this condition were considered to be independent events. The oxygen therapy could not be masked, but the investigators remained blinded until outcome data were locked. The primary outcome was successful anaesthesia without interruption of the surgical procedure for rescue oxygenation. A rescue oxygenation event was defined as an interruption of the surgical procedure to deliver positive pressure ventilation using either bag mask technique, insertion of an endotracheal tube, or laryngeal mask to improve oxygenation. There were ten secondary outcomes, including the proportion of procedures with a hypoxaemic event (SpO2 <90%). Analyses were done on an intention-to-treat (ITT) basis. Safety was assessed in all enrolled participants. This trial is registered in the Australian New Zealand Clinical Trials Registry, ACTRN12618000949280, and is completed. FINDINGS: From Sept 4, 2018, to April 12, 2021, 581 procedures in 487 children were randomly assigned to high-flow oxygen (297 procedures) or standard care (284 procedures); after exclusions, 528 procedures (267 assigned to high-flow oxygen and 261 assigned to standard care) in 483 children (293 male and 190 female) were included in the ITT analysis. The primary outcome of successful anaesthesia without interruption for tubeless airway surgery was achieved in 236 (88%) of 267 procedures on high-flow oxygen and in 229 (88%) of 261 procedures on standard care (adjusted risk ratio [RR] 1·02, 95% CI 0·96-1·08, p=0·82). There were 51 (19%) procedures with a hypoxaemic event in the high-flow oxygen group and 57 (22%) in the standard care group (RR 0·86, 95% CI 0·58-1·24). Of the other prespecified secondary outcomes, none showed a significant difference between groups. Adverse events of epistaxis, laryngospasm, bronchospasm, hypoxaemia, bradycardia, cardiac arrest, hypotension, or death were similar in both study groups. INTERPRETATION: Nasal high-flow oxygen during tubeless upper airway surgery did not reduce the proportion of interruptions of the procedures for rescue oxygenation compared with standard care. There were no differences in adverse events between the intervention groups. These results suggest that both approaches, nasal high-flow or standard oxygen, are suitable alternatives to maintain oxygenation in children undergoing upper airway surgery. FUNDING: Thrasher Research Fund, the Australian and New Zealand College of Anaesthetists, the Society for Paediatric Anaesthesia in New Zealand and Australia.

Flexible bronchoscopy insufflated and high-flow nasal oxygen pilot trial (BUFFALO protocol pilot trial).

BACKGROUND: Hypoxaemia occurs in approximately 30% of children during anaesthesia for flexible bronchoscopy. High-flow nasal oxygen (HFNO) can prolong safe apnoea time and be used in children with abnormal airways. During flexible bronchoscopy, there is limited evidence if HFNO confers advantages over current standard practice in avoiding hypoxaemia. The aim is to investigate feasibility of HFNO use during anaesthesia for flexible bronchoscopy to reduce frequency of rescue oxygenation and hypoxaemia. METHODS: BUFFALO is a bi-centre, unmasked, randomised controlled, parallel group, protocol for a pilot trial comparing HFNO techniques to standard practice during anaesthesia. Children (n = 81) aged > 37 weeks to 16 years presenting for elective bronchoscopy who fulfil inclusion but not exclusion criteria will be randomised prior to the procedure to HFNO or standard care oxygenation post induction of anaesthesia. Maintenance of anaesthesia with HFNO requires total venous anaesthesia (TIVA) and with standard, either inhalational or TIVA at discretion of anaesthetist in charge of the patient. Outcomes will include the feasibility of recruitment and adherence to trial procedures, acceptability of the intervention of the protocol and completion rates of data collection methods. DISCUSSION: Findings of this trial will determine feasibility to plan for a larger multicentre randomised clinical trial and support the feasibility of the proposed study procedures. TRIAL REGISTRATION: BUFFALO trial was registered with Australia and New Zealand Clinical Trials Registry (TRN12621001635853) on 29 November 2021 and commenced recruitment in May 2022. https://www.anzctr.org.au/ . The primary manuscript will be submitted for publication in a peer-reviewed journal.

Transnasal Humidified Rapid Insufflation Ventilatory Exchange in children requiring emergent intubation (Kids THRIVE): a statistical analysis plan for a randomised controlled trial.

The placement of an endotracheal tube for children with acute or critical illness is a low-frequency and high-risk procedure, associated with high rates of first-attempt failure and adverse events, including hypoxaemia. To reduce the frequency of these adverse events, the provision of oxygen to the patient during the apnoeic phase of intubation has been proposed as a method to prolong the time available for the operator to insert the endotracheal tube, prior to the onset of hypoxaemia. However, there are limited data from randomised controlled trials to validate the efficacy of this technique in children. The technique known as transnasal humidified rapid insufflation ventilatory exchange (THRIVE) uses high oxygen flow rates (approximately 2 L/kg/min) delivered through nasal cannulae during apnoea. It has been shown to at least double the amount of time available for safe intubation in healthy children undergoing elective surgery. The technique and its application in real time have not previously been studied in acutely ill or injured children presenting to the emergency department or admitted to an intensive care unit. The Kids THRIVE trial is a multicentre, international, randomised controlled trial (RCT) in children less than 16 years old undergoing emergent intubation in either the intensive care unit or emergency department of participating hospitals. Participants will be randomised to receive either the THRIVE intervention or standard care (no apnoeic oxygenation) during their intubation. The primary objective of the trial is to determine if the use of THRIVE reduces the frequency of oxygen desaturation and increases the frequency of first-attempt success without hypoxaemia in emergent intubation of children compared with standard practice. The secondary objectives of the study are to assess the impact of the use of THRIVE on the rate of adverse events, length of mechanical ventilation and length of stay in intensive care. In this paper, we describe the detailed statistical analysis plan as an update of the previously published protocol.

Consumer research priorities for pediatric anesthesia and perioperative medicine.

BACKGROUND: Consumer-driven research is increasingly being prioritized. AIM: Our aim was to partner with consumers to identify the top 10 research priorities for pediatric anesthesia and perioperative medicine. The ACORN (Anesthesia Consumer Research Network) was formed to collaborate with children and families across Australia. METHODS: A prospective online survey was developed to generate research ideas from consumers. The survey was developed in Qualtrics, a survey research platform. Consumers were invited to participate through poster advertising, social media posts, via consumer networks at participating hospitals and in addition 35 national consumer/patient representative organizations were approached. We also conducted a similar idea generating survey for clinicians through email invitation and via Twitter. A second round of surveys was conducted to prioritize the long list of research questions and a shortlist of priorities developed. A single consensus meeting was held, and a final consensus list of top 10 priorities emerged. RESULTS: A total of 281 research ideas were submitted between 356 consumers in the idea generating survey and from four consumer/patient representative groups. Seventy-five clinicians responded to the clinician idea generation survey. This was consolidated into 20 research ideas/themes for the second survey for each group. 566 responses were received to the consumer prioritization top 10 survey and 525 responses to the clinician survey. The consensus meeting produced the final 10 consumer research priorities. CONCLUSION: This study has given Australian consumers the opportunity to shape the anesthesia and perioperative medicine research agenda for pediatric patients both nationally and internationally.

Apnoeic oxygenation during paediatric intubation: A systematic review.

Objective: This review assesses the effect of apnoeic oxygenation during paediatric intubation on rates of hypoxaemia, successful intubation on the first attempt and other adverse events. Data sources: The databases searched included PubMed, Medline, CINAHL, EMBASE and The Cochrane Library. An electronic search for unpublished studies was also performed. Study selection: We screened studies that include children undergoing intubation, studies that evaluate the use of apnoeic oxygenation by any method or device with outcomes of hypoxaemia, intubation outcome and adverse events were eligible for inclusion. Data extraction: Screening, risk of bias, quality of evidence and data extraction was performed by two independent reviewers, with conflicts resolved by a third reviewer where consensus could not be reached. Data synthesis: From 362 screened studies, fourteen studies (N = 2442) met the eligibility criteria. Randomised controlled trials (N = 482) and studies performed in the operating theatre (N = 835) favoured the use of apnoeic oxygenation with a reduced incidence of hypoxaemia (RR: 0.34, 95% CI: 0.24 to 0.47, p < 0.001, I 2 = 0% and RR: 0.27, 95% CI: 0.11 to 0.68, p = 0.005, I 2 = 68% respectively). Studies in the ED and PICU were of lower methodological quality, displaying heterogeneity in their results and were unsuitable for meta-analysis. Among the studies reporting first attempt intubation success, there were inconsistent effects reported and data were not suitable for meta-analysis. Conclusion: There is a growing body of evidence to support the use of apnoeic oxygenation during the intubation of children. Further research is required to determine optimal flow rates and delivery technique. The use of humidified high-flow oxygen shows promise as an effective technique based on data in the operating theatre, however its efficacy has not been shown to be superior to low flow oxygen in either the elective anesthetic or emergency intubation situations Systematic Review Registration: This review was prospectively registered in the PROSPERO international register of systematic reviews (Reference: CRD42020170884, registered April 28, 2020).

Developing an Extubation strategy for the difficult pediatric airway-Who, when, why, where, and how?

Comprehensive airway management of the pediatric patient with a difficult airway requires a plan for the transition back to a patent and protected airway. Multiple techniques are available to manage the periextubation period. Equally important is performing a comprehensive risk assessment and developing a strategy that optimizes the likelihood of safe extubation. This includes team-focused communication of the desired goals, critical steps in the process, and potential responses in the case of failed extubation. This review summarizes extubation of pediatric patients with difficult airways along with one suggested framework to manage this challenging period.

Understanding pediatric ventilation in the operative setting. Part II: Setting perioperative ventilation.

Approaches toward lung-protective ventilation have increasingly been investigated in recent years. Despite evidence being found in adults undergoing surgery, data in younger children are still scarce and controversial. From a physiological perspective, however, the continuously changing characteristics of the respiratory system from birth through adolescence require an approach based on the analysis of each individual patient. The modern anesthesia workstation provides such information, with the technical strengths and weaknesses being discussed in a review preceding the present work (see Part I). The present summary aims to provide ideas on how to translate the information displayed on the anesthesia workstation to patient-oriented clinical ventilation settings.

Understanding pediatric ventilation in the operative setting. Part I: Physical principles of monitoring in the modern anesthesia workstation.

The modern anesthesia workstation provides a wealth of information some of which is of particular interest when it comes to optimizing ventilation settings. This knowledge gains even more importance in the therapy of pediatric patients. In the absence of evidence-based recommendations on optimal ventilation settings in pediatric patients, the evaluation of individual factors becomes crucial and challenging at the same time. Even when equipped with the latest sensor technology, the user will always have to be in charge of interpreting the provided monitoring variables. The purpose of this review is to outline the clinical impact, technological background, and reliability of the most relevant information measured and calculated by a modern anesthesia workstation. It aims at translating the technical knowledge into a more competent and vigilant application in the clinical setting.

Carbon dioxide monitoring in children-A narrative review of physiology, value, and pitfalls in clinical practice.

Continuous capnography has been recognised as an essential monitoring device in all anesthetized patients, despite which airway device is in use, regardless of their location, as a measure to improve patient safety. Capnography is the non-invasive measurement of a sample of the exhaled carbon dioxide which has multiple clinical uses including as a method to confirm placement of a tracheal tube and/or to assess ventilation, perfusion and metabolism. Notably, capnography is used during routine paediatric anesthesia to assess ventilation and as a surrogate measure for arterial carbon dioxide pressure. The inaccuracies associated with these surrogate measures need to be considered to inform improved ventilation management of infants and children. This review highlights some major principles to understand the carbon dioxide elimination, the physiology of paediatric capnography, the clinical application and the limitations of capnography during anesthesia for neonates, infants and small children.

Pediatric Thromboelastograph 6s and Laboratory Coagulation Reference Values.

CONTEXT.­: Specific reference intervals (RIs) facilitate accurate interpretation of results. Coagulation assay results may vary by demographics and also between reagents and analyzers used. Current Thromboelastograph 6s (TEG 6s) Hemostasis Analyzer RIs were generated from adult samples. OBJECTIVE.­: To generate reagent analyzer-specific pediatric RIs for TEG 6s and coagulation parameters. DESIGN.­: A prospective, observational, single-center study of healthy children undergoing general anesthesia (January 3, 2017 to January 3, 2019). Venous blood samples were obtained for TEG 6s (Kaolin, Kaolin-Heparinase, Rapid and Functional Fibrinogen assays) and coagulation parameters (activated partial thromboplastin time, prothrombin time, thrombin clotting time, Echis time, antithrombin activity, and fibrinogen concentration using Instrumentation Laboratory ACL-TOP analyzers). Differences between activated partial thromboplastin time and prothrombin time reagents were investigated using mixed-effects regression, comparing maximum coefficients-of-variation with assay-specific allowable variation. RIs (lower/upper limits 2.5th of 97.5th percentiles) were generated using the following 2 methods: within discrete age-groups (neonates [<1 month], infants [1 month-1 year], young children [1-5 years], older children [6-10 years], and adolescents [11-16 years]), and modeled as functions of age and/or sex using quantile regression, including significant fractional polynomial and interaction terms. RESULTS.­: Variation between prothrombin time and activated partial thromboplastin time assays using different reagents was clinically significant. Reagent-analyzer specific pediatric RIs were generated using data from 254 children. Discrete and model-based RIs varied by age for all coagulation parameters and TEG 6s variables in all assays. CONCLUSIONS.­: We report reagent-analyzer specific pediatric RIs for TEG 6s and coagulation parameters. Observed variation reinforces recommendations for laboratory-specific RIs. These findings improve accuracy of interpretation of clinical results, provide a foundation for comparison and validation of tests in pathology, and illustrate feasibility and advantages of model-based RI approaches.

Nasal high-flow oxygen in pediatric anesthesia and airway management.

Nasal High-Flow (NHF) is weight-dependent in children, aimed to match peak inspiratory flow and thereby deliver an accurate FiO2 with a splinting pressure of 4-6 cm H2 O. During apnea in children, NHF oxygen can double the expected time to desaturation below 90% in well children but there is no ventilatory exchange; therefore, children do not "THRIVE". Total intravenous anesthesia competency to maintain spontaneous breathing is an important adjunct for successful NHF oxygenation technique during anesthesia. Jaw thrust to maintain a patent upper airway is paramount until surgical instrumentation occurs. There is no evidence to support safe use of NHF oxygen with LASER use due to increased risk of airway fire.

High-flow oxygen for children's airway surgery: randomised controlled trial protocol (HAMSTER).

INTRODUCTION: Hypoxaemia during anaesthesia for tubeless upper airway surgery in children with abnormal airways is common due to the complexity of balancing adequate depth of anaesthesia with maintenance of spontaneous breathing and providing an uninterrupted field of view of the upper airway for the surgeon. High-flow nasal oxygenation (HIGH-FLOW) can prolong safe apnoea time and be used in children with abnormal airways but to date has not been compared with the alternative technique of low-flow nasal oxygenation (LOW-FLOW). The aim is to investigate if use of HIGH-FLOW can reduce the number of hypoxaemic events requiring rescue oxygenation compared with LOW-FLOW. METHODS AND ANALYSIS: High-flow oxygen for children's airway surgery: randomised controlled trial (HAMSTER) is a multicentre, unmasked, randomised controlled, parallel group, superiority trial comparing two oxygenation techniques during anaesthesia. Children (n=530) aged >37 weeks to 16 years presenting for elective tubeless upper airway surgery who fulfil inclusion but not exclusion criteria will be randomised prior to surgery to HIGH-FLOW or LOW-FLOW post induction of anaesthesia. Maintenance of anaesthesia with HIGH-FLOW requires Total IntraVenous Anaesthesia (TIVA) and with LOW-FLOW, either inhalational or TIVA at discretion of anaesthetist. The primary outcome is the incidence of hypoxaemic events requiring interruption of procedure for rescue oxygenation by positive pressure ventilation and the secondary outcome includes total hypoxaemia time, adverse cardiorespiratory events and unexpected paediatric intensive care admission admission. Hypoxaemia is defined as Sp02 <90%. Analysis will be conducted on an intention-to-treat basis. ETHICS AND DISSEMINATION: Ethical approval has been obtained by Children's Health Queensland Human Research Ethics Committee (HREC/18/QRCH/130). The trial commenced recruitment in 2018. The primary manuscript will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: The HAMSTER is registered with the Australia and New Zealand Clinical TrialsRegistry: ACTRN12618000949280.

Transnasal Humidified Rapid Insufflation Ventilatory Exchange in children requiring emergent intubation (Kids THRIVE): a protocol for a randomised controlled trial.

INTRODUCTION: Emergency intubation of children with abnormal respiratory or cardiac physiology is a high-risk procedure and associated with a high incidence of adverse events including hypoxemia. Successful emergency intubation is dependent on inter-related patient and operator factors. Preoxygenation has been used to maximise oxygen reserves in the patient and to prolong the safe apnoeic time during the intubation phase. Transnasal Humidified Rapid Insufflation Ventilatory Exchange (THRIVE) prolongs the safe apnoeic window for a safe intubation during elective intubation. We designed a clinical trial to test the hypothesis that THRIVE reduces the frequency of adverse and hypoxemic events during emergency intubation in children and to test the hypothesis that this treatment is cost-effective compared with standard care. METHODS AND ANALYSIS: The Kids THRIVE trial is a multicentre randomised controlled trial performed in participating emergency departments and paediatric intensive care units. 960 infants and children aged 0-16 years requiring emergency intubation for all reasons will be enrolled and allocated to THRIVE or control in a 1:1 allocation with stratification by site, age (<1, 1-7 and >7 years) and operator (junior and senior). Children allocated to THRIVE will receive weight appropriate transnasal flow rates with 100% oxygen, whereas children in the control arm will not receive any transnasal oxygen insufflation. The primary outcomes are defined as follows: (1) hypoxemic event during the intubation phase defined as SpO2 <90% (patient-dependent variable) and (2) first intubation attempt success without hypoxemia (operator-dependent variable). Analyses will be conducted on an intention-to-treat basis. ETHICS AND DISSEMINATION: Ethics approval for the protocol and consent process has been obtained (HREC/16/QRCH/81). The trial has been actively recruiting since May 2017. The study findings will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ACTRN12617000147381.

Nasal high-flow oxygen delivery in children with abnormal airways.

BACKGROUND: Transnasal Humidified Rapid-Insufflation Ventilatory Exchange has been shown to safely prolong the safe apnea time in well children post induction of anesthesia and is rapidly becoming a new standard for apneic oxygenation in adults. The same oxygenation technique is described as nasal high flow and can be used in infants and children at risk of apnea during anesthesia. AIM: We investigated the use of nasal high flow oxygen delivery during anesthesia in children with abnormal airways requiring tubeless airway assessment or surgery. METHODS: Data and outcomes of pediatric patients receiving nasal high flow for upper airway procedures were analyzed. Four categories were defined: (i) tubeless airway surgery, (ii) flexible bronchoscopy, (iii) expected difficult airway, and (iv) comorbidity related risk of apnea. Anesthesia was induced intravenously or with sevoflurane (4-8%) and then converted to total intravenous anesthesia aiming for spontaneous ventilation. Age appropriate nasal high flow cannulae were secured with 100% oxygen delivery at weight-related flow rates. Topicalization of the airway was achieved with lignocaine. Complication rates of desaturation requiring interruption of procedure for rescue oxygenation were recorded. RESULTS: Twenty children were analyzed with age range of 5 days to 11 years, ASA 1-4, and weight range 3-57 kg. Fifteen were induced with sevoflurane and 100% oxygen, five received total intravenous anesthesia only. All children received Optiflow™ nasal high flow and intravenous anesthesia during their procedure. Average SpO2 recorded was 96% with lowest SpO2 77%. One required rescue oxygenation. Median length of procedure was 32 min, (range 3-61). Most common indication was tubeless airway surgery but seven children had more than one indication. CONCLUSION: Nasal high flow can be used in spontaneously breathing children with abnormal airways for maintenance of oxygenation during anesthesia for tubeless airway procedures.

Increased brain tissue oxygen tension in children with traumatic brain injury using temperature-corrected guided ventilation during prophylactic hypothermia.

OBJECTIVE: To investigate whether ventilatory management using a temperature-corrected (pH-stat) or uncorrected (alpha-stat) blood gas analysis strategy improves brain tissue oxygen tension (PbrO(2)) in children prophylactically treated with moderate hypothermia for traumatic brain injury. DESIGN, SETTING AND PARTICIPANTS: Double crossover study conducted in the intensive care unit of a tertiary children's hospital. Nine children aged 3-14 years with severe traumatic brain injury were randomly allocated twice to a 6-hour period of either alpha- or pH-stat management while being kept hypothermic at 32.5°C. MAIN OUTCOME MEASURES: PbrO(2), intracranial pressure (ICP) and PbrO(2)/PaO(2). RESULTS: PbrO(2) was significantly higher during pH-stat management (alpha-stat, 23.2mmHg [95% CI, 22.4- 24.0mmHg] v pH-stat, 28.7mmHg [95% CI, 27.9- 29.5mmHg]; P < 0.001). PbrO(2)/PaO(2) was significantly higher during pH-stat (alpha-stat, 0.190 [95% CI, 0.187- 0.193] v pH-stat, 0.251 [95% CI, 0.246-0.259]; P < 0.05). ICP was non-significantly higher during pH-stat (alpha-stat, 8.8mmHg [95% CI, 8.1-9.5mmHg] v ph-stat,10.2mmHg [95% CI, 9.6-10.8]). CONCLUSION: PbrO(2) may be improved using a pH-stat blood gas management strategy in prophylactic hypothermia for paediatric patients with traumatic brain injury without any clinically relevant increase in ICP.

The effect of induction of anesthesia and intubation on end-expiratory lung level and regional ventilation distribution in cardiac children.

BACKGROUND: During the induction of anesthesia, changes in functional residual capacity and ventilation distribution (VD) occur. Although these physiological changes are well investigated in adults, little data are available in infants and children. AIM: To describe continuous changes in lung physiology during the induction of anesthesia in infants and children using electrical impedance tomography (EIT). METHODS: Lung mechanics and volume changes in 38 infants and children undergoing elective cardiac surgery were assessed using EIT before, during, and after the induction of anesthesia. End-expiratory level (EEL as an equivalent to FRC) and VD were measured with EIT and referenced to a period of spontaneous breathing prior to induction. RESULTS: EEL changed significantly during induction with the lowest during the intubation phase and normalized with the application of positive end-expiratory pressures (PEEP) after induction. Ventilation prior to induction was preferentially distributed toward the dependent lung, whereas after induction, the nondependent lung was better ventilated. PEEP during mechanical ventilation did not improve ventilation inhomogeneity. CONCLUSION: Lung volume and mechanics deteriorate significantly during the induction of anesthesia and remain altered during mechanical ventilation.